Lee Seung-Tae, Kim Jee-Ah, Jang Shin-Yi, Kim Duk-Kyung, Do Young Soo, Suh Gee Young, Kim Jong-Won, Ki Chang-Seok
Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
J Korean Med Sci. 2009 Feb;24(1):69-76. doi: 10.3346/jkms.2009.24.1.69. Epub 2009 Feb 28.
Hereditary hemorrhagic telangiectasia (HHT) is an inherited disorder that is characterized by abnormal communication between the arteries and veins in the skin, mucosa, and various organs. HHT has been reported to show significant phenotypic variability and genetic heterogeneity with wide ethnic and geographic variations. Although mutations in the endoglin (ENG) and activin A receptor type II-like 1 (ACVRL1) genes have been known to cause HHT for more than 10 yr, little is known about the clinical features or genetic background of Korean patients with HHT. In addition, mutations in mothers against decapentaplegic homolog 4 (SMAD4) are also seen in patients with the combined syndrome of juvenile polyposis and HHT. This study examined five Korean patients with the typical manifestations of HHT such as frequent epistaxis and pulmonary arteriovenous malformations. Direct sequencing of the ENG and ACVRL1 genes revealed one known mutation, ENG c.277C>T, in one patient and two novel mutations, ENG c.992-1G>C and ACVRL1 c.81dupT in two patients, respectively. The remaining two patients with negative results were screened for SMAD4 mutations as well as gross deletions of ENG and ACVRL1 using multiple ligation-dependent probe amplification, but none was detected. Despite the small number of patients investigated, we firstly report Korean patients with genetically confirmed HHT, and show the genetic and allelic heterogeneity underlying HHT.
遗传性出血性毛细血管扩张症（HHT）是一种遗传性疾病，其特征是皮肤、黏膜和各种器官中的动静脉之间存在异常连通。据报道，HHT表现出显著的表型变异性和遗传异质性，存在广泛的种族和地理差异。尽管已知内皮糖蛋白（ENG）和激活素A受体II型样1（ACVRL1）基因的突变在10多年前就已被证实可导致HHT，但对于韩国HHT患者的临床特征或遗传背景却知之甚少。此外，在青少年息肉病和HHT联合综合征患者中也发现了母亲对脱磷酸化蛋白同源物4（SMAD4）的突变。本研究对5例具有HHT典型表现（如频繁鼻出血和肺动静脉畸形）的韩国患者进行了检查。对ENG和ACVRL1基因进行直接测序，结果显示1例患者存在一个已知突变ENG c.277C>T，另外2例患者分别存在两个新突变ENG c.992-1G>C和ACVRL1 c.81dupT。对其余2例结果为阴性的患者，使用多重连接依赖探针扩增技术筛查了SMAD4突变以及ENG和ACVRL1的大片段缺失，但均未检测到。尽管研究的患者数量较少，但我们首次报告了基因确诊的韩国HHT患者，并展示了HHT潜在的遗传和等位基因异质性。
